title: Role of the CD137 ligand (CD137L) signaling pathway during Mycobacterium tuberculosis infection.
abstract: The role of the CD137-CD137 ligand (CD137L) signaling pathway in T cell co-stimulation has been well established. Dysregulated CD137 or CD137L stimulation can lead to pathological conditions such as inflammatory diseases or cancer. However, the contribution of CD137-CD137L interaction to the control of infectious diseases has not been extensively studied, with the few available reports focusing mainly on viral infections. Here we investigated the role of the CD137-CD137L interactions during Mycobacterium tuberculosis infection. Using CD137L-deficient mice, we found that absence of the CD137L-mediated signaling pathway during M. tuberculosis infection resulted in delayed activation of CD4(+) T cells in the draining lymph nodes. This finding was supported by an in vitro mixed lymphocyte reaction assay that revealed impaired priming of T cells by CD137L-deficient dendritic cells upon mycobacterial infection. In addition, greater numbers of CD4(+) T cells and antigen presenting cells were measured in the lungs of CD137L-deficient mice. Strikingly, the lung cytokine production profile was profoundly altered in M. tuberculosis-infected CD137L-deficient mice with lower levels of TNF-α, IL-12 and IL-6 and elevated concentrations of IL-17 compared to their wild type counterparts. However and surprisingly, these tangible immunological disorders translated only into a mild and transient increase in the bacterial loads and a higher number of granulomatous lesions with impaired architecture in the lungs of the CD137L-deficient infected mice. Together, while our data support the engagement of the CD137L signaling pathway during M. tuberculosis infection, they underscore the functional redundancy and robustness of the host defense arsenal deployed against mycobacterial infection.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Julia María
authors.initials: JM
authors.lastname: Martínez Gómez
authors.forename: Vanessa Hui Qi
authors.initials: VH
authors.lastname: Koh
authors.forename: Benedict
authors.initials: B
authors.lastname: Yan
authors.forename: Wenwei
authors.initials: W
authors.lastname: Lin
authors.forename: Michelle Lay Teng
authors.initials: ML
authors.lastname: Ang
authors.forename: Siti Zarina Zainul
authors.initials: SZ
authors.lastname: Rahim
authors.forename: Kevin
authors.initials: K
authors.lastname: Pethe
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
mesh_terms: D053330:4-1BB Ligand / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D053330:4-1BB Ligand; D016207:Cytokines; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Adaptive immunity; CD137–CD137L interactions; Granuloma; Tuberculosis